Conversion Rate of Abstracts Presented at Plastic Surgery The Meeting From 2010 to 2019: A 10-Year Analysis of Factors for Success.

BACKGROUND: Presentations are an important means of knowledge generation. Publication of these studies is important for dissemination of findings beyond meeting attendees. We analyzed a 10-year sample of presented abstracts at Plastic Surgery The Meeting and describe factors that improve rate and speed of conversion to peer-reviewed publication. METHODS: Abstracts presented between 2010 and 2019 at Plastic Surgery The Meeting were sourced from the American Society of Plastic Surgery Abstract Archive. A random sample of 100 abstracts from each year was evaluated. Abstract information and demographics were recorded. The title or author and keywords of each abstract were searched using a standardized workflow to find a corresponding published paper on PubMed, Google Scholar, and Google. Data were analyzed for trends and factors affecting conversion rate. RESULTS: A total of 983 presented abstracts were included. The conversion rate was 54.1%. Residents and fellows constituted the largest proportion of presenters (38.4%). There was a significant increase in medical student and research fellow presenters during the study period (P < 0.001). Conversion rate was not affected by the research rank of a presenter's affiliated institution (ß = 1.001, P = 0.89), geographic location (P = 0.60), or subspecialty tract (P = 0.73). US academics had a higher conversion rate (61.8%) than US nonacademics (32.7%) or international presenters (47.1%) (P < 0.001). Medical students had the highest conversion rate (65.6%); attendings had the lowest (45.0%). Research fellows had the lowest average time to publication (11.6 months, P = 0.007). CONCLUSIONS: Lower levels of training, factors associated with increased institution-level support, and research quality affect rate and time to publication. These findings highlight the success of current models featuring medical student and research fellow-led projects with strong resident and faculty mentorship.

Mycobacterium tuberculosis Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti-Mtb Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 µM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.

A tool for assessing the comprehensiveness of outcome reporting within clinical trials in pregnancy.

INTRODUCTION: Clinical trials provide fundamental evidence used to inform healthcare decisions at patient- and population levels and it is thus important that trials consider outcomes relevant to both patients and stakeholders. Although validated tools assessing other aspects of trial integrity exist, there is no tool for assessing the breadth and completeness of outcomes measured. Our objective was to develop a comprehensiveness of outcome reporting (COR) tool to assess this within trials in pregnancy. MATERIAL AND METHODS: We developed a tool that aids in visualizing outcome reporting through the automatic generation of a heatmap, enabling assessment of the range of maternal and fetal/neonatal outcomes included in clinical trials. Outcome reporting and measurement of each study is compared to a context-specific, user-determined, ideal standard set of outcomes, created by initially considering all domains within five core outcome areas. These include mortality, morbidity, functioning/life-impact, resource-use, and adverse events, as identified by the most recent taxonomy for outcomes in medical research. We tested the tool's functionality using trials previously identified as studies on obesity in pregnant patients, and further compared the utility of the COR Tool against Cochrane's Risk of Bias 2.0 Tool using correlational analysis. RESULTS: The pilot heatmap using clinical trials studying obesity in pregnancy (n = 15), illustrated a lack of comprehensiveness of reported outcomes in the majority of studies. Included trials were found to readily report physiological/clinical outcome but consistently neglected outcome areas related to functioning, delivery of care, resource-use, and adverse events. Outcome areas reported and measured were done so with largely varying degrees of quality. When the COR Tool was compared with Cochrane's RoB 2.0 Tool on a scatter plot, only a weak correlation was found (R = 0.2936, R2  = 0.0862) CONCLUSIONS: The COR Tool will promote transparency in clarifying what outcomes a trial's conclusions are based on, encourage trialists to consider outcomes related to all aspects of maternal and fetal/neonatal health, and support reviewers in appraising outcome reporting and measurement in the assessment of trial integrity. Used in tandem with RoB tools and core outcome sets, we hope the COR Tool will meaningfully contribute to improving maternal-infant health.

The effect of COVID-19 pandemic on the care of fragility hip fracture patients in the United Kingdom. A case control study in a major trauma centre.

INTRODUCTION: Coronavirus disease 2019 is a pandemic that forced a transformation in the services provided by the National Health Service in the United Kingdom. Fragility hip fractures account for over 65,000 cases per year in the elderly population. The study aims to assess the impact of the pandemic on fragility hip fractures. METHODS: A retrospective data gather was performed to identify fragility hip fractures from the 23rd of March 2020 to the 13th of May 2020, and from the 23rd of March 2019 to the 13th of May 19. Two groups were formed and compared over their 30 day follow up. RESULTS: The control group comprised of 97 patients, with a mean age of 82.1 years old (62-102 years) and M:F ratio of 38:59. The case group comprised of 102 patients, with a mean age of 82.3 years old (60-100 years) and a M:F ratio of 16:86. Significant differences between groups were identified for gender (p < 0.001), time to theatre (p = 0.002), length of stay (p < 0.001) and COVID-19 status (p = 0.001). In the Case group, association with mortality was found for male gender (p = 0.041), right side (p = 0.031) and COVID-19 positive test results (p = 0.011). CONCLUSION: Early surgical intervention is advocated wherever possible, and sufficient optimisation, prior to surgery whenever a COVID-19 positive patient is identified. A safe rehabilitation environment is paramount for recovery in this group of patients. Further studies are required to understand the effect of this pandemic on the fragility hip fractures. LEVEL OF EVIDENCE: Level III: Retrospective case-control study.

Pelvic and acetabular fracture management in intravenous drug users.

INTRODUCTION: Pelvic and acetabular fractures are significant injuries associated with high morbidity or mortality. Intravenous drug users (IVDU) represent a challenging group of patients, with an increased risk of complications and infection. To our knowledge there has not been any published literature concerning IVDU and this type of injuries. PATIENTS AND METHODS: A group of 19 patients with a history of IVDU and who had sustained an injury were identified. RESULTS: The mean age at injury was 36 years old; nine had a pelvic fracture and ten had an acetabular fracture. No complications were observed in the pelvic group. In the acetabular group, the infection risk was 50% and the risk of femoral head avascular necrosis was 33%. The mean follow up was 43.1 months from injury. CONCLUSION: We advise emphasis in the high infection and avascular necrosis rates, when consenting the patient for an operation. Furthermore, non-operative treatment should be considered, where possible. LEVEL OF EVIDENCE: Level III. Retrospective cohort study. Prognostic-investigating the effect of a patient characteristic on the outcome of the disease.

Evaluating risk factors following surgery for periprosthetic fractures around hip and knee arthroplasties.

BACKGROUND: The increasing demand for arthroplasty has resulted in an inevitable rise in the number of periprosthetic fractures around implants. Survival factors looking into patient's comorbidities and how they influence outcome are rare. This study aims to identify correlations between survival post-injury and pre-existing comorbidities. METHODS: A total of 144 patients underwent operative treatment for either a hip or a knee periprosthetic fracture from January 2008 to August 2017 at our Major Trauma Hospital. The mean age at injury was 80.9 years old (SD 9.9). Each patient had a case-based analysis to ascertain injury characteristics, operative parameters and comorbidities. RESULTS: The mean survival was 12.7 months (95% CI 8.4-17.1). Survival analysis showed a correlation between age more than 75 years old (p = 0.001), ASA grade of 3 or higher (p = 0.009 Breslow's test), history of CVA or TIA (p = 0.038 Breslow's test), dementia (p = 0.002 log rank test), depression (p = 0.013 log rank test) and gender (p = 0.041, Breslow's test) and survival post-periprosthetic fracture. Survival within the first year following injury was found to be affected by the presence of osteoporosis (p = 0.020) and dementia (p = 0.002). CONCLUSION: Periprosthetic fractures are associated with a high mortality risk (34.7%). Operative risks can be minimised with careful optimisation and surgical planning. ASA, age and comorbidities (dementia, CVA or TIA, osteoporosis) have a significant correlation with survival post-injury. Hence, careful patient selection for operative treatment is advised.

An outbreak of Salmonella Saintpaul gastroenteritis after attending a school camp in the Northern Territory, Australia.

An outbreak of salmonellosis occurred following attendance at a school camp between 5 and 8 August 2014 in a remote area of the Northern Territory, Australia. We conducted a retrospective cohort study via telephone interviews, using a structured questionnaire that recorded symptoms and exposures to foods and activities during the camp. A case was anyone with laboratory confirmed Salmonella Saintpaul infection or a clinically compatible illness after attending the camp. Environmental health officers from the Environmental Health Branch undertook an investigation and collected water and environmental samples. We interviewed 65 (97%) of the 67 people who attended the camp. There were 60 students and 7 adults. Of the 65 people interviewed, 30 became ill (attack rate 46%); all were students; and 4 had laboratory confirmed S. Saintpaul infection. The most commonly reported symptoms were diarrhoea (100% 30/30), abdominal pain (93% 28/30), nausea (93% 28/30) and fever (70% 21/30). Thirteen people sought medical attention but none required hospitalisation. Illness was significantly associated with drinking cordial at lunch on 7 August (RR 3.8, 95% CI 1.3-11, P < 0.01), as well as drinking cordial at lunch on 8 August (RR 2.1, 95% CI 1.1-4.2, P=0.01). Salmonella spp. was not detected in water samples or wallaby faeces collected from the camp ground. The epidemiological investigation suggests the outbreak was caused by environmental contamination of food or drink and could have occurred during ice preparation or storage, preparation of the cordial or from inadequate sanitising of the cooler from which the cordial was served. This outbreak highlights the risks of food or drink contamination with environmental Salmonella. Those preparing food and drink in campground settings should be vigilant with cleaning, handwashing and disinfection to prevent outbreaks of foodborne disease.

An outbreak of salmonellosis associated with duck prosciutto at a Northern Territory restaurant.

In June 2015, an outbreak of salmonellosis occurred among people who had eaten at a restaurant in Darwin, Northern Territory over 2 consecutive nights. We conducted a retrospective cohort study of diners who ate at the restaurant on 19 and 20 June 2015. Diners were telephoned and a questionnaire recorded symptoms and menu items consumed. An outbreak case was defined as anyone with laboratory confirmed Salmonella Typhimurium PT9 (STm9) or a clinically compatible illness after eating at the restaurant. Environmental health officers inspected the premises and collected food samples. We contacted 79/83 of the cohort (response rate 95%); 21 were cases (attack rate 27%), and 9 had laboratory confirmed STm9 infection. The most commonly reported symptoms were diarrhoea (100%), abdominal pain (95%), fever (95%) and nausea (95%). Fifteen people sought medical attention and 7 presented to hospital. The outbreak was most likely caused by consumption of duck prosciutto, which was consumed by all cases (OR 18.6, CI 3.0-∞, P < 0.01) and was prepared on site. Salmonella was not detected in any food samples but a standard plate count of 2 x 107 colony forming units per gram on samples of duck prosciutto demonstrated bacterial contamination. The restaurant used inappropriate methodology for curing the duck prosciutto. Restaurants should consider purchasing pre-made cured meats, or if preparing them on site, ensure that they adhere to safe methods of production.

Systemic exposure to and disposition of catechols derived from Salvia miltiorrhiza roots (Danshen) after intravenous dosing DanHong injection in human subjects, rats, and dogs.

DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses ≥10 µmol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection.

A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome.

PURPOSE: The Muir-Torre syndrome variant of Lynch syndrome is characterized by the presence of sebaceous neoplasms (adenoma, epithelioma/sebaceoma, carcinoma) and Lynch syndrome-associated cancers (colon, endometrial, and others). Several clinical scoring systems have been developed to identify patients with colon cancer at high risk of Lynch syndrome. However, no such system has been described for patients presenting with sebaceous neoplasms. METHODS: Based on logistic regression analysis, a scoring system was developed for patients with sebaceous neoplasm to identify those with the highest likelihood of having Muir-Torre syndrome. The final version of the scoring system included variables such as age at presentation of initial sebaceous neoplasm, total number of sebaceous neoplasms, personal history of a Lynch-related cancer, and family history of Lynch-related cancers. RESULTS: Patients with a score of 3 or more were more likely to have Muir-Torre syndrome (28 of 29 patients), those with a score of 2 had intermediate likelihood (12 of 20 patients), and no patient with a score of 0 or 1 was diagnosed with Muir-Torre syndrome. CONCLUSION: The Mayo Muir-Torre syndrome risk scoring system appears to identify whether patients who present with sebaceous neoplasms are in need of further Lynch syndrome evaluation using easily ascertained clinical information. Abnormal mismatch repair gene immunohistochemistry of a sebaceous neoplasm is a poor predictor in regard to diagnosing Lynch syndrome.

Reactive Oxygen Species Modulation in the Current Landscape of Anticancer Therapies.

Significance: Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism, and are tightly controlled through homeostatic mechanisms to maintain intracellular redox, regulating growth and proliferation in healthy cells. However, ROS production is perturbed in cancers where abnormal accumulation of ROS leads to oxidative stress and genomic instability, triggering oncogenic signaling pathways on one hand, while increasing oxidative damage and triggering ROS-dependent death signaling on the other. Recent Advances: Our review illuminates how critical interactions between ROS and oncogenic signaling, the tumor microenvironment, and DNA damage response (DDR) pathways have led to interest in ROS modulation as a means of enhancing existing anticancer strategies and developing new therapeutic opportunities. Critical Issues: ROS equilibrium exists via a delicate balance of pro-oxidant and antioxidant species within cells. "Antioxidant" approaches have been explored mainly in the form of chemoprevention, but there is insufficient evidence to advocate its routine application. More progress has been made via the "pro-oxidant" approach of targeting cancer vulnerabilities and inducing oxidative stress. Various therapeutic modalities have employed this approach, including direct ROS-inducing agents, chemotherapy, targeted therapies, DDR therapies, radiotherapy, and immunotherapy. Finally, emerging delivery systems such as "nanosensitizers" as radiotherapy enhancers are currently in development. Future Directions: While approaches designed to induce ROS have shown considerable promise in selectively targeting cancer cells and dealing with resistance to conventional therapies, most are still in early phases of development and challenges remain. Further research should endeavor to refine treatment strategies, optimize drug combinations, and identify predictive biomarkers of ROS-based cancer therapies.

Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components.

Exosomes are small extracellular 40-100 nm diameter membrane vesicles of late endosomal origin that can mediate intercellular transfer of RNAs and proteins to assist premetastatic niche formation. Using primary (SW480) and metastatic (SW620) human isogenic colorectal cancer cell lines we compared exosome protein profiles to yield valuable insights into metastatic factors and signaling molecules fundamental to tumor progression. Exosomes purified using OptiPrep™ density gradient fractionation were 40-100 nm in diameter, were of a buoyant density ~1.09 g/mL, and displayed stereotypic exosomal markers TSG101, Alix, and CD63. A major finding was the selective enrichment of metastatic factors (MET, S100A8, S100A9, TNC), signal transduction molecules (EFNB2, JAG1, SRC, TNIK), and lipid raft and lipid raft-associated components (CAV1, FLOT1, FLOT2, PROM1) in exosomes derived from metastatic SW620 cells. Additionally, using cryo-electron microscopy, ultrastructural components in exosomes were identified. A key finding of this study was the detection and colocalization of protein complexes EPCAM-CLDN7 and TNIK-RAP2A in colorectal cancer cell exosomes. The selective enrichment of metastatic factors and signaling pathway components in metastatic colon cancer cell-derived exosomes contributes to our understanding of the cross-talk between tumor and stromal cells in the tumor microenvironment.

Proteomic analysis of the oil palm fruit mesocarp reveals elevated oxidative phosphorylation activity is critical for increased storage oil production.

Palm oil is a highly versatile commodity with wide applications in the food, cosmetics, and biofuel industries. Storage oil in the oil palm mesocarp can make up a remarkable 80% of its dry mass, making it the oil crop with the richest oil content in the world. As such, there has been an ongoing interest in understanding the mechanism of oil production in oil palm fruits. To identify the proteome changes during oil palm fruit maturation and factors affecting oil yield in oil palm fruits, we examined the proteomic profiles of oil palm mesocarps at four developing stages--12, 16, 18, and 22 weeks after pollination--by 8-plex iTRAQ labeling coupled to 2D-LC and MALDI-TOF/TOF MS. It was found that proteins from several important metabolic processes, including starch and sucrose metabolism, glycolysis, pentose phosphate shunt, fatty acid biosynthesis, and oxidative phosphorylation, were differentially expressed in a concerted manner. These increases led to an increase in carbon flux and a diversion of resources such as ATP and NADH that are required for lipid biosynthesis. The temporal proteome profiles between the high-oil-yielding (HY) and low-oil-yielding (LY) fruits also showed significant differences in the levels of proteins involved in the regulation of the TCA cycle and oxidative phosphorylation. In particular, the expression level of the ß subunit of the ATP synthase complex (complex IV of the electron transport chain) was found to be increased during fruit maturation in HY but decreased in the LY during the fruit maturation. These results suggested that increased energy supply is necessary for augmented oil yield in the HY oil palm trees.

Living Alone, Environmental Hazards, and Falls Among U.S. Older Adults.

Background and Objectives: Physical conditions of living environments can affect the incidence of falls; however, prior work has focused typically on 1 domain at a time-either neighborhood or home, capturing limited environmental boundaries of older adults. We examined how neighborhood together with the home environment affect the incidence of falls over time and whether living arrangement modifies the influence of the environmental risks on falls. Research Design and Methods: Using the 2012-2020 waves of the Health and Retirement Study (HRS; N = 1,893), we fitted logistic regression to estimate the incidence of falls over an 8-year study period. We used the neighborhood and housing data that are collected systematically by trained observers in the HRS to assess environmental hazards. Sidewalk quality, neighborhood disorder, and the presence of green space were measured to capture outdoor environmental hazards. Indoor environmental hazards included the presence of housing decay and poorly maintained stairways. All models were stratified by living arrangement. Results: Neighborhood and housing environment were independently associated with the odds of falls net of demographic characteristics and preexisting health conditions, and effects were significant for people living alone only. The presence of green space and poorly maintained stairways were associated with greater odds of falling, net of covariates during 8 years of follow-up (odds ratios = 2.10 and 2.65, p < .05, respectively). None of the environmental risk factors were significant for those living with others. Discussion and Implications: Falls in old age may be determined in part by a combination of outdoor and indoor risk factors. More research is needed to understand pathways that lead to greater vulnerability among older adults living alone to environmental hazards.

Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses.

TnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. We searched genomes of diverse eukaryotes and their viruses for TnpB homologs and identified numerous putative RNA-guided nucleases that are often associated with various transposases, suggesting they are encoded in mobile genetic elements. Reconstruction of the evolution of these nucleases, which we rename Horizontally-transferred Eukaryotic RNA-guided Mobile Element Systems (HERMES), revealed multiple acquisitions of TnpBs by eukaryotes and subsequent diversification. In their adaptation and spread in eukaryotes, HERMES proteins acquired nuclear localization signals, and genes captured introns, indicating extensive, long term adaptation to functioning in eukaryotic cells. Biochemical and cellular evidence show that HERMES employ non-coding RNAs encoded adjacent to the nuclease for RNA-guided cleavage of double-stranded DNA. HERMES nucleases contain a re-arranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that HERMES can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.

Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2.

Cells respond to perturbations such as inflammation by sensing changes in metabolite levels. Especially prominent is arginine, which has known connections to the inflammatory response. Aminoacyl-tRNA synthetases, enzymes that catalyse the first step of protein synthesis, can also mediate cell signalling. Here we show that depletion of arginine during inflammation decreased levels of nuclear-localized arginyl-tRNA synthetase (ArgRS). Surprisingly, we found that nuclear ArgRS interacts and co-localizes with serine/arginine repetitive matrix protein 2 (SRRM2), a spliceosomal and nuclear speckle protein, and that decreased levels of nuclear ArgRS correlated with changes in condensate-like nuclear trafficking of SRRM2 and splice-site usage in certain genes. These splice-site usage changes cumulated in the synthesis of different protein isoforms that altered cellular metabolism and peptide presentation to immune cells. Our findings uncover a mechanism whereby an aminoacyl-tRNA synthetase cognate to a key amino acid that is metabolically controlled during inflammation modulates the splicing machinery.

Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses.

Programmable RNA-guided DNA nucleases perform numerous roles in prokaryotes, but the extent of their spread outside prokaryotes is unclear. Fanzors, the eukaryotic homolog of prokaryotic TnpB proteins, have been detected in genomes of eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. Here, we characterize Fanzors as RNA-programmable DNA endonucleases, using biochemical and cellular evidence. We found diverse Fanzors that frequently associate with various eukaryotic transposases. Reconstruction of Fanzors evolution revealed multiple radiations of RuvC-containing TnpB homologs in eukaryotes. Fanzor genes captured introns and proteins acquired nuclear localization signals, indicating extensive, long-term adaptation to functioning in eukaryotic cells. Fanzor nucleases contain a rearranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that Fanzors can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.